BOSTONLaboratory studies assessing the effect of potent
thalidomide analogs on multiple myeloma cells suggest they have
potential for the treatment of multiple myeloma, investigators from
Dana-Farber Cancer Institute and Harvard Medical School reported.
Among the analogs tested were three immunomodulatory drugs (IMiDs),
being developed by Celgene Corporation (Warren, NJ). These agents
markedly stimulate T-cell proliferation as well as interleukin-2
(IL-2) and interferon-gamma production.
Kenneth C. Anderson, MD, of Dana-Farber Cancer Institute, reported
that all three of the IMiDs tested were found to be dose-dependent
inhibitors of multiple myeloma cells from human multiple myeloma cell
lines and from myeloma patients (Blood 96:2943-2950, 2000).
The IMiDs were also effective against cell lines resistant to
conventional antimyeloma agents, including doxorubicin, mitoxantrone
(Novantrone), melphalan (Alkeran), and dexamethasone. Furthermore,
combination treatment with dexamethasone and IMiDs significantly
improved inhibition of multiple myeloma cell line proliferation.
The studies showed that IMiDs act directly against human multiple
myeloma cells by inducing apoptosis or G1 growth arrest,
the researchers said.
These results provide the framework for the development and
testing of a new biologically based treatment paradigm that uses
these novel agents, either alone or together with conventional
therapies, to target both the tumor cell and its microenvironment,
overcome classical drug resistance, and achieve improved outcomes in
this presently incurable disease, the investigators concluded.